Polymeric molecular conductors are known. For example, some naturally occurring proteins facilitate electron transfer in such fundamental biological processes as photosynthesis and respiration. Electron transfer in such systems is generally understood to occur as the result of quantum mechanical ‘tunnelling’ of electrons along pathways, molecular orbitals, that connect one atom to the next in the polymer.
It has been proposed that the stacked aromatic bases of DNA may act as a ‘π-way’ for the transfer of electrons (Dandliker et al., 1997; Hall et al., 1996; Arkin et al., 1996). This proposal is based on a theory that the stacked arrangement of bases on complementary strands juxtaposes the shared electrons in the π orbitals of the aromatic nitrogen bases, facilitating quantum mechanical tunnelling along the stack of base pairs. A number of experiments have supported the view that this effect exists, while other experiments have provided contrary evidence that the effect is limited or non-existent.
For example, experiments have been reported to demonstrate that photoinduced electron transfer may occur between two metallointercalators tethered at either end of a 15-base pair DNA duplex (Murphy et al., 1993). On the other hand, kinetic analysis of distance-dependent electron transfer in a DNA hairpin has been used to show that DNA is a poor conductor, only somewhat more effective than proteins as a conductor of electrons (Lewis et al., 1997; Taubes 1997).
U.S. Pat. Nos. 5,591,578; 5,705,348; 5,770,369; 5,780,234 and 5,824,473 issued to Meade et al. on, respectively, 7 Jan. 1997, 6 Jan. 1998, 23 June 1998, 14 Jul. 1998 and 20 Oct. 1998 (and incorporated herein by reference) disclose nucleic acids that are covalently modified with electron transfer moieties along the nucleic acid backbone. Meade et al. teach that such modifications are necessary for nucleic acids to efficiently mediate electron transfer.
The theory of π-orbital-mediated conductance along a nucleic acid duplex suggests that, as a precondition, such conductance requires a stable duplex with stacked base pairs. The effect on duplex stability of the binding of metal ions to nucleic acids, particularly DNA, has been studied extensively for nearly 40 years. In general, cations that bind primarily to the phosphate backbone will stabilize the duplex conformation, whereas those that bind to the bases will tend to denature the duplex. These effects are readily demonstrated with thermal denaturation profiles (Tm measurements). Experiments of this sort show that most monovalent cations, such as Na+, which tend to interact with the phosphate backbone, stabilize the duplex. This effect is reflected in the finding that there is approximately a 12° C. increase in Tm for each 10-fold increase in monovalent cation concentration (Marmur and Doty 1962). An exception to this general principle is Ag+, which binds tightly to nitrogen bases, destabilizes the duplex, and therefore decreases the duplex Tm (Guay and Beauchamp 1979). Similarly, multivalent ions, particularly polyamines, which interact with the phosphate backbone are very effective duplex stabilizers.
For divalent metal cations, a series can be written in increasing order of DNA destabilization: Mg2+, Co2+, Ni2+, Mn2+, Zn2+, Cd2+, Cu2+ (Eichorn 1962; Eichorn and Shin 1968). At one end of the spectrum, Mg2+ increases the Tm at all concentrations; at the other end of the spectrum, sufficiently high concentrations of Cu2+ will lead to complete denaturation of the duplex at room temperature (Eichorn and Shin 1968). This series also correlates with the ability of the divalent cations to bind to the bases (Hodgson 1977; Swaminathan and Sundaralingham 1979).
Cations are also involved in promoting several other structural transitions and dismutations in nucleic acids. It has previously been reported that Zn2+ and some other divalent metal ions bind to duplex DNA at pHs above 8 and cause a conformational change (Lee et al., 1993). Preliminary characterization of the resulting structure incorporating zinc showed that it retained two antiparallel strands but that it was distinct from normal ‘B’ DNA: it did not bind ethidium bromide, it appeared to lose the imino protons of both A-T and G-C base pairs upon addition of a stoichiometric amount of Zn2+, and it contained at least 5% fewer base pairs per turn than ‘B’ DNA.